Wild-type vesicular stomatitis virus (VSV) replicates to high titer in BHK-21 cells in vitro and in vivo in brains and spinal cords of intracerebrally (i.c.) infected mice. Both in vitro and in vivo, wild-type VSV infection is highly cytocidal. Certain temperature-sensitive (ts) mutants, principally ts G31 and ts G22, produce a slowly progressive central nervous system (CNS) disease after i.c. inoculation. On the other hand, other ts mutants, i.e. tsG11 or tsG41, are avirulent. Accompanying the slowly progressive CNS disease induced by ts G31 and G22, are marked spongiogorm changes in spinal cords of affected mice. The spongioform myelopathy appears almost exclusively in grey matter and is centered primarily in neurons, astrocytes and neuronal processes. Ts virus is recoverable from affected spinal cords coincident with demonstration of the histopathological lesions. In addition, i.c. infection with homologous defective-interfering (DI) particles and wild-type VSV also results in a slowly progressive and invariably fatal CNS disease. Current plans include study in the pathogenesis of slowly progressive CNS disease induced by certain ts mutants of VSV as well as homologous DI particles and wild-type and/or ts mutants of VSV. Approaches will include: (1) a sequential study of infection in mice produced by wild-type VSV, or ts G31 or ts G22 VSV, or homologous DI particle-wild-type VSV and/or ts mutant VSV; (2) sequential virological, histopathological and immunofluorescent studies in CNS infection produced by these viruses; and (3) an analysis of the biochemical defects in ts RNA and viral protein synthesis as they may relate to altered CNS disease and histopathological lesions observed. BIBLIOGRAPHIC REFERENCES: Rabinowitz, S.G., Dal Canto, M.C. Comparison of Central Nervous System Disease Produced by Wild-Type and Temperature-Sensitive Mutants of Vesicular Stomatitis Virus. Infec. Immun. 13: 1242-1249, 1976. Dal Canto, M.C., Rabinowitz, S.G., and Johnson, T.C. Status Spongiosus Resulting from Intracerebral Infection with Temperature-Sensitive Mutants of Vesicular Stomatitis Virus. Br. J. Exp. Path. 57: 321-330, 1976.